How quantum entanglement in DNA synchronizes double-strand breakage by type II restriction endonucleases.

Macroscopic quantum effects in living systems have been studied widely in pursuit of fundamental explanations for biological energy transport and sensing. While it is known that type II endonucleases, the largest class of restriction enzymes, induce DNA double-strand breaks by attacking phosphodiester bonds, the mechanism by which simultaneous cutting is coordinated between the catalytic centers remains unclear. We propose a quantum mechanical model for collective electronic behavior in the DNA helix, where dipole-dipole oscillations are quantized through boundary conditions imposed by the enzyme. Zero-point modes of coherent oscillations would provide the energy required for double-strand breakage. Such quanta may be preserved in the presence of thermal noise by the enzyme's displacement of water surrounding the DNA recognition sequence. The enzyme thus serves as a decoherence shield. Palindromic mirror symmetry of the enzyme-DNA complex should conserve parity, because symmetric bond-breaking ceases when the symmetry of the complex is violated or when physiological parameters are perturbed from optima. Persistent correlations in DNA across longer spatial separations-a possible signature of quantum entanglement-may be explained by such a mechanism.

Study of the use of antidepressants for depression in dementia: the HTA-SADD trial--a multicentre, randomised, double-blind, placebo-controlled trial of the clinical effectiveness and cost-effectiveness of sertraline and mirtazapine.

OBJECTIVE: Depression is common in dementia, causing considerable distress and other negative impacts. Treating it is a clinical priority, but the evidence base is sparse and equivocal. This trial aimed to determine clinical effectiveness of sertraline and mirtazapine in reducing depression 13 weeks post randomisation compared with placebo. DESIGN: Multicentre, parallel-group, double-blind placebo-controlled randomised controlled trial of the clinical effectiveness of sertraline and mirtazapine with 13- and 39-week follow-up. SETTING: Nine English old-age psychiatry services. PARTICIPANTS: A pragmatic trial. Eligibility: probable or possible Alzheimer's disease (AD), depression (4+ weeks) and Cornell Scale for Depression in Dementia (CSDD) score of 8+. EXCLUSIONS: clinically too critical (e.g. suicide risk); contraindication to medication; taking antidepressants; in another trial; and having no carer. INTERVENTIONS: (1) Sertraline; (2) mirtazapine; and (3) placebo, all with normal care. Target doses: 150 mg of sertraline or 45 mg of mirtazapine daily. OUTCOME: CSDD score. Randomisation: Allocated 1 : 1 : 1 through Trials Unit, independently of trial team. Stratified block randomisation by centre, with randomly varying block sizes; computer-generated randomisation. Blinding: Double blind: medication and placebo identical for each antidepressant. Referring clinicians, research workers, participants and pharmacies were blind. Statisticians blind until analyses completed. RESULTS: Numbers randomised: 326 participants randomised (111 placebo, 107 sertraline and 108 mirtazapine). OUTCOME: Differences in CSDD at 13 weeks from an adjusted linear-mixed model: mean difference (95% CI) placebo-sertraline 1.17 (-0.23 to 2.78; p = 0.102); placebo-mirtazapine 0.01 (-1.37 to 1.38; p = 0.991); and mirtazapine-sertraline 1.16 (-0.27 to 2.60; p = 0.112). HARMS: Placebo group had fewer adverse reactions (29/111, 26%) than sertraline (46/107, 43%) or mirtazapine (44/108, 41%; p = 0.017); 39-week mortality equal, five deaths in each group. CONCLUSIONS: This is a trial with negative findings but important clinical implications. The data suggest that the antidepressants tested, given with normal care, are not clinically effective (compared with placebo) for clinically significant depression in AD. This implies a need to change current practice of antidepressants being the first-line treatment of depression in AD. From the data generated we formulated the following recommendations for future work. (1) The secondary analyses presented here suggest that there would be value in carrying out a placebo-controlled trial of the clinical effectiveness and cost-effectiveness of mirtazapine in the management of Behavioural and Psychological Symptoms of Dementia. (2) A conclusion from this study is that it remains both ethical and essential for trials of new medication for depression in dementia to have a placebo arm. (3) Further research is required to evaluate the impact that treatments for depression in people with dementia can have on their carers not only in terms of any impacts on their quality of life, but also the time they spend care-giving. (4) There is a need for research into alternative biological and psychological therapies for depression in dementia. These could include evaluations of new classes of antidepressants (such as venlafaxine) or antidementia medication (e.g. cholinesterase inhibitors). (5) Research is needed to investigate the natural history of depression in dementia in the community when patients are not referred to secondary care services. (6) Further work is needed to investigate the cost modelling results in this rich data set, investigating carer burden and possible moderators to the treatment effects. (7) There is scope for reanalysis of the primary outcome in terms of carer and participant CSDD results.

Turning principles into practice in Alzheimer's disease.

The prevalence of dementia is reaching epidemic proportions globally, but there remain a number of issues that prevent people with dementia, their families and caregivers, from taking control of their condition. In 2008, Alzheimer's Disease International (ADI) launched a Global Alzheimer's Disease Charter, which comprises six principles that underscore the urgency for a more ambitious approach to diagnosis, treatment and care. This review highlights some of the most important aspects and challenges of dementia diagnosis and treatment. These issues are reviewed in light of the six principles of the recent ADI Charter: promoting dementia awareness and understanding; respecting human rights; recognizing the key role of families and caregivers; providing access to health and social care; stressing the importance of optimal diagnosis and treatment; and preventing dementia through improvements in public health. The authors continue to hope that, one day, a cure for Alzheimer's disease will be found. Meanwhile, healthcare professionals need to unite in rising to the challenge of managing all cases of dementia, using the tools available to us now to work toward improved patient care.

Alcohol in moderation, premorbid intelligence and cognition in older adults: results from the Psychiatric Morbidity Survey.

AIMS: To test the hypothesis that the association previously reported between moderate alcohol use and better cognition is an artefact of confounding by (a) higher premorbid education and socioeconomic status; (b) a lifestyle of moderation (using smoking as a risk marker); and (c) decreased alcohol consumption in people with physical illnesses. METHOD: Data were analysed from people aged 60-74 years interviewed for the 2000 British National Psychiatric Morbidity Survey, representative of people living in private homes. Alcohol use information was available for 1985 (98.9%) of the eligible participants, of whom 1735 (87.4%) who drank moderately or abstained were included in the analyses. Our main outcome measures were the Alcohol Use Disorders Identification Test (AUDIT), the Telephone Interview for Cognitive Status Screen for Cognitive Impairment and the National Adult Reading Test to measure crystallised (premorbid) intelligence. Our physical health measures were the number of prescribed medications and physical illness reported, and the 12 item Short Form Health Survey's Physical Component Score. RESULTS: The relationship between current cognition and alcohol use was reduced and no longer significant after considering premorbid intelligence or physical health. In our final model, the significant predictors of current cognition among non-problem drinkers were: age (B = -0.13, -0.18 to -0.08; p<0.001) and crystallised intelligence (B = 0.14, 0.12 to 0.17; p<0.001). Smoking was not associated with cognition. CONCLUSIONS: In people who were not problem drinkers, higher alcohol intake was not associated with improved current cognition after controlling for premorbid intelligence and physical health. Our findings suggest that, despite previous suggestions, moderate alcohol consumption does not protect older people from cognitive decline.

Effects of individualized memory aids on the conversation of persons with severe dementia: a pilot study.

Bourgeois has shown that use of simple memory aids enhances the quality of conversation of persons with moderate Alzheimer-type dementia. We replicated Bourgeois' intervention with five people with severe dementia (Mini-Mental State Examination scores 0-4) and diagnoses of Alzheimer-type or vascular dementia, and evaluated the impact of the aids on the proportion of time participants spent on topic in conversation with carers. For three participants, use of the memory aid did not increase the proportion of time-spent on-topic. The remaining two participants, however, spent approximately twice as much time on-topic when using the aid as when conversing without it. Our results extend Bourgeois' work by showing that memory aids are helpful to some people with severe dementia.

Best place of care for older people after acute and during subacute illness: a systematic review.

OBJECTIVES: To assess the evaluative research literature on the costs, quality and effectiveness of different locations of care for older patients. METHODS: A systematic review of evaluative research from 1988 using CRD4 guidelines. Twenty-five databases were searched, using processes developed specially for this review. Library OPACS, the Internet and research registers were also searched for relevant material. The final stage of the review was confined to randomised and pseudorandomised trials. Studies were selected for review by pairs of researchers working independently who then met to reach a decision. Analysis was predominantly descriptive; simple pooled odds ratios were used to explore some outcomes. RESULTS: Eighty-four papers from 45 trials were included. Firm conclusions were difficult to draw, except in relation to some outcomes for stroke units, early discharge schemes and geriatric assessment units. Few trials in this area have adequately addressed issues of patients' quality of life and costs to health services, social care providers, patients and their families. CONCLUSIONS: Despite considerable recent development of different forms of care for older patients, evidence about effectiveness and costs is weak. However, evidence is also weak for longer-standing care models. A substantial service evaluation agenda emerges from this review. This study also raises questions about the usefulness of systematic review techniques in the area of service delivery and organisation.

Modeling and observations of phase-mask trapezoidal profiles with grating-fiber image reproduction.

We report on an investigation of the trapezoidal design and fabrication defects in phase masks used to produce Bragg reflection gratings in optical fibers. We used a direct visualization technique to examine the nonuniformity of the interference patterns generated by several phase masks. Fringe patterns from the phase masks are compared with the analogous patterns resulting from two-beam interference. Atomic force microscope imaging of the actual phase gratings that give rise to anomalous fringe patterns is used to determine input parameters for a general theoretical model. Phase masks with pitches of 0.566 and 1.059 microm are modeled and investigated.

The concept of delirium.

The concept of delirium has a long and confusing history. This article outlines the development of ideas relating to core features of the syndrome: disturbance of consciousness, disturbance of cognition, its course and its external causation. The modern concept of delirium, and the diagnostic criteria found in current classifications are based upon a long tradition of clinical observation in younger patients, and their emphasis on positive symptoms and identifiable external causes may not be applicable to our ageing population.

Studies of suicide in later life: methodologic considerations and research directions.

Later-life suicide is a tragedy that occurs worldwide. Often it is preventable. Here, the authors summarize an international workshop where they review four research approaches to studying putative risk factors: epidemiologic studies of suicidal behaviors, clinic-based follow-up studies, studies of suicide attempters, and psychological autopsy studies. They provide brief descriptions of the approaches, examples of questions best addressed by each approach, and their weaknesses and limitations; they also recommend promising areas for future research and propose opportunities for research that could be conducted cross-nationally.

Using an annual over-75 health check to screen for depression: validation of the short Geriatric Depression Scale (GDS15) within general practice.

OBJECTIVE: To validate the short Geriatric Depression Scale (GDS15) as a screening instrument and determine the optimal cutpoint for detecting depression among older people living in the community. DESIGN: Two stage study with the first stage consisting of a health check of people aged 75 years and over by a practice nurse which included the GDS15. A second-stage diagnostic interview including the criterion standard was carried out blind to GDS15 score. SETTING: A large general practice in Melton Mowbray, Leicestershire, UK. PATIENTS: A random sample (stratified according to first-stage GDS15 score) of 257 older people living in the community, without significant cognitive impairment, were selected for the second-stage diagnostic interview. MEASURES: The first-stage GDS15 score was compared with diagnostic status for depression and anxiety disorders (according to ICD-10 criteria) and presence of depressive symptoms at the second-stage clinical interview. RESULTS: Ninety-three per cent of those eligible for the study were successfully screened with the GDS15. A cutpoint of <3/3+ had a sensitivity of 100% and specificity of 72% in detecting cases of depression but fewer than one in five of those testing positive reached a diagnostic threshold. Only 25% of those with a diagnosis of depression had any mention of mental health problems in their medical notes in the year prior to the clinical interview. For detecting depressive symptoms the same cutpoint was 79% sensitive and 78% specific with a positive predictive value of 46%. CONCLUSIONS: Used as part of an annual over-75 health check in primary care, the GDS15 would detect a significant amount of hidden morbidity which would serve the original purpose of the annual elderly health checks in the UK.

The FEAR: a rapid screening instrument for generalized anxiety in elderly primary care attenders.

OBJECTIVE: To develop a shorter version of the Anxiety Disorder Scale (ADS) for use as a rapid screening instrument in primary care. DESIGN: Two-stage screening design. Primary care attenders aged 65 and over were screened for generalized anxiety in the surgery with the 11-item generalized anxiety subscale of the ADS (ADS GA), a selected subsample then proceeding to a clinical validation interview. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Scores on the ADS GA, non-hierarchical ICD-10 caseness for generalized anxiety established by brief clinical interview by an old age psychiatrist. RESULTS: The prevalence rate of generalized anxiety was 16% using the established cutpoint and showed an age-related decline. A cutpoint of 2-3/11 appeared to give optimal performance in this small sample (sensitivity 85%, specificity 77%, positive predictive value 52%), suggesting that 36% of elderly general practice attenders might be diagnosed as having generalized anxiety. A reduced four-item version gave a predicted sensitivity of 77%, a specificity of 83% and a positive predictive value of 63% (cutpoint 1-2/4). CONCLUSIONS: A four-item version of the ADS GA, the FEAR (frequency of anxiety; enduring nature of anxiety; alcohol or sedative use; restlessness or fidgeting), has potential as a rapid screening instrument for use in primary care.

Formation of phase gratings on the end of gradient-index lenses with ultraviolet ablation at 193 nm.

We present a simple, cost-effective method for creating diffractive optical elements on the surfaces of optical fibers and fiber-optic components by use of 193-nm ablation techniques. It is an outgrowth of a more fundamental investigation of the effects of intense UV radiation fields on SiO2- and Ge-SiO2-based structures (specifically optical fibers and preforms) and allows the inexpensive fabrication of structures such as the suggested evanescent-field-based sensing device.

Is the diagnosis of dementia stable over time among elderly immigrant Gujaratis in the United Kingdom (Leicester)?

BACKGROUND: The single largest ethnic elder group in the United Kingdom originates from the Indian subcontinent and their numbers are increasing. METHOD: Elderly Gujarati subjects, with a diagnosis of dementia ascertained during an epidemiological field study in Leicester, were reexamined at a median follow-up interval of 27 months to establish stability of the original diagnosis and cognitive decline. RESULTS: Seven of the original 11 subjects with dementia were alive at the follow-up and they were reexamined by a Gujarati psychiatrist. In six of these seven subjects the diagnosis of dementia was reconfirmed with concomitant cognitive decline on the CAMDEX dementia severity index. Informant history in three of the four original dementia subjects provided evidence of cognitive decline between the original interview and death. CONCLUSION: The diagnosis of dementia in elderly Gujaratis was stable at follow-up with concurrent evidence of decline. This also provided further support for the validity and performance of the Gujarati MMSE in the original study.

Assessment of patients with memory problems using a nurse-administered instrument to detect early dementia and dementia subtypes.

BACKGROUND: With the development of pharmacological treatments for Alzheimer's disease there will be an increase in the numbers of patients requiring assessment from specialist services. Could the role of the specialist clinician be supported by other health professionals screening those who might benefit from treatment? METHOD: Sixty-four consecutive referrals to the Leicester University Memory Clinic were assessed at home by a community psychiatric nurse using a semi-structured interview. The nurse then reported her findings to a psychiatrist and a diagnosis was agreed. This diagnosis was then compared to the Memory Clinic diagnosis and a standardized (ICD-10) diagnosis recorded by another psychiatrist examining the clinic records. RESULTS: The nurse assessment procedure performed well in detecting dementia, with a kappa statistic (k) of 0.75 when compared to the standardized and Memory Clinic diagnoses. There was, however, only moderate concordance between the ICD-10 diagnosis and nurse (k = 0.46) and the Memory Clinic and nurse (k = 0.60) for Alzheimer's disease. The relatively low k value for Alzheimer's disease was principally a result of difficult in differentiating vascular dementia. CONCLUSIONS: A single supervised community psychiatric nurse, using a structured assessment instrument, can adequately detect early dementia in a sample of patients referred with memory problems. Subtypes of dementia are not, however, accurately differentiated.

Gender and interactions between care staff and elderly nursing home residents with dementia.

OBJECTIVE: This study explores the relationship between gender and the interactions of care staff and elderly people with dementia in residential care. DESIGN: Non-participant, time-sampling observation and coding of interactions between staff and residents. SETTING: 36-bed independent (not-for-profit) long-term care unit. SUBJECTS: 36 elderly people with dementia (19 men and 17 women); 37 care staff (30 women and 7 men). MEASURES: The Quality of Interactions Schedule (QUIS). RESULTS: Male residents initiated significantly more interactions with staff than female residents. Men did not initiate interactions with female staff significantly more often than with male staff. Women did not initiate any interactions with male staff. Female staff initiated more interactions with residents than did male staff. Both male and female staff initiated a higher proportion of interactions with male residents than with female residents. CONCLUSIONS: These findings suggest that gender may be a significant factor determining the rate of interactions between staff and residents in residential care, but further studies are required to confirm their generalizability across settings.

Knowledge, uptake and availability of health and social services among Asian Gujarati and white elderly persons.

OBJECTIVES: To investigate factors affecting the uptake of health and social services by elderly Asian Gujarati. METHODS: Four hundred and five Hindu Gujaratis and 381 whites aged 65 years and over residing in Leicester were randomly sampled from the Leicestershire District FHSA list by a computerized method based on linguistic analysis of the patient's name. One hundred and fifty Hindu Gujaratis and 152 whites were interviewed with response rates of 72% for the Asian Gujaratis and 80% for the white groups. The outcome measures were the activities of daily living (ADLs), incontinence, auditory/ visual deficits, cardiovascular disease, cognitive impairment (measured by the Mini-mental State Examination), depression, use of GP and hospital services, knowledge of community health and social services, willingness to use, suitability and cultural accessibility. RESULTS: The poorer uptake of services by elderly Asian Gujarati could not be explained by better health. They were significantly more likely to be dependent in six of the 14 ADLs and had higher rates of diabetes and impaired vision. Significantly more Asian Gujaratis than whites lived with others (84 versus 52%, p < 0.0001) with a greater availability of alternative sources of help and support. The knowledge and understanding of services were significantly poorer in the Gujarati group; fewer Asian Gujaratis knew how to apply for services and of those applying, fewer had been successful. Where services had been obtained, the levels of dissatisfaction were higher in the Gujarati group. The literacy rates were low in the Gujarati sample with 79% being unable to read or write in English and 27% unable to read or write in their mother tongue. CONCLUSIONS: The lower uptake of services by elderly Asian Gujarati is not the result of better health but may be explained by greater family support together with a lack of knowledge of and dissatisfaction with what is available. Health services will need to reappraise and revise some of their practices if they are to cater adequately for this growing population with many needs as yet unmet.